SANDESTIN, FLA. – New forms of IgG4 testing could be more helpful in making diagnoses of immunoglobulin G4-related disease, an expert said at the annual Congress of Clinical Rheumatology, while cautioning that the diagnosis is more about histology and pattern of involvement than antibody testing.

Arezou Khosroshahi, MD, of Emory University, Atlanta, said that the IgG4 levels found in serum using nephelometry can often be low in patients who otherwise show signs of the disease, which can affect a wide array of organs and typically involves elevated IgG4. Newer forms of testing – enzyme-linked ImmunoSpot (ELISPOT) and quantitative reverse transcription polymerase chain reaction (RT-qPCR) – could be more telling, she said.

Perhaps even better, studies in Europe have found that RT-qPCR testing for IgG4 RNA can be effective. This type of testing is easier than ELISPOT, and “they are finding the sensitivity to be much superior to nephelometry for immunoglobulin levels,” Dr. Khosroshahi said.

The higher the levels of IgG4, the more likely an IgG4-related disease diagnosis is warranted, and higher levels tend to lead to worse outcomes, she said.

She waved a caution flag, though: Other diseases can involve elevated IgG4, and even a normal IgG4 level does not necessarily rule out the disease. Other evaluations really form the cornerstone of the diagnosis of IgG4-related disease, she said.

“There should be characteristic histology and of course IgG4-staining, but more importantly, pattern of organ involvement. It’s very important,” Dr. Khosroshahi said. “If there is a mass in the pancreas and there is salivary gland and parotid gland swellings and other features of that going on, you are more concerned that that is a process going on.”

Dr. Khosroshahi had no relevant disclosures.

SANDESTIN, FLA. – New forms of IgG4 testing could be more helpful in making diagnoses of immunoglobulin G4-related disease, an expert said at the annual Congress of Clinical Rheumatology, while cautioning that the diagnosis is more about histology and pattern of involvement than antibody testing.

Arezou Khosroshahi, MD, of Emory University, Atlanta, said that the IgG4 levels found in serum using nephelometry can often be low in patients who otherwise show signs of the disease, which can affect a wide array of organs and typically involves elevated IgG4. Newer forms of testing – enzyme-linked ImmunoSpot (ELISPOT) and quantitative reverse transcription polymerase chain reaction (RT-qPCR) – could be more telling, she said.

Perhaps even better, studies in Europe have found that RT-qPCR testing for IgG4 RNA can be effective. This type of testing is easier than ELISPOT, and “they are finding the sensitivity to be much superior to nephelometry for immunoglobulin levels,” Dr. Khosroshahi said.

The higher the levels of IgG4, the more likely an IgG4-related disease diagnosis is warranted, and higher levels tend to lead to worse outcomes, she said.

She waved a caution flag, though: Other diseases can involve elevated IgG4, and even a normal IgG4 level does not necessarily rule out the disease. Other evaluations really form the cornerstone of the diagnosis of IgG4-related disease, she said.

“There should be characteristic histology and of course IgG4-staining, but more importantly, pattern of organ involvement. It’s very important,” Dr. Khosroshahi said. “If there is a mass in the pancreas and there is salivary gland and parotid gland swellings and other features of that going on, you are more concerned that that is a process going on.”

Dr. Khosroshahi had no relevant disclosures.

SANDESTIN, FLA. – New forms of IgG4 testing could be more helpful in making diagnoses of immunoglobulin G4-related disease, an expert said at the annual Congress of Clinical Rheumatology, while cautioning that the diagnosis is more about histology and pattern of involvement than antibody testing.

Arezou Khosroshahi, MD, of Emory University, Atlanta, said that the IgG4 levels found in serum using nephelometry can often be low in patients who otherwise show signs of the disease, which can affect a wide array of organs and typically involves elevated IgG4. Newer forms of testing – enzyme-linked ImmunoSpot (ELISPOT) and quantitative reverse transcription polymerase chain reaction (RT-qPCR) – could be more telling, she said.

Perhaps even better, studies in Europe have found that RT-qPCR testing for IgG4 RNA can be effective. This type of testing is easier than ELISPOT, and “they are finding the sensitivity to be much superior to nephelometry for immunoglobulin levels,” Dr. Khosroshahi said.

The higher the levels of IgG4, the more likely an IgG4-related disease diagnosis is warranted, and higher levels tend to lead to worse outcomes, she said.

She waved a caution flag, though: Other diseases can involve elevated IgG4, and even a normal IgG4 level does not necessarily rule out the disease. Other evaluations really form the cornerstone of the diagnosis of IgG4-related disease, she said.

“There should be characteristic histology and of course IgG4-staining, but more importantly, pattern of organ involvement. It’s very important,” Dr. Khosroshahi said. “If there is a mass in the pancreas and there is salivary gland and parotid gland swellings and other features of that going on, you are more concerned that that is a process going on.”

Dr. Khosroshahi had no relevant disclosures.

I am not sure when it occurred. I don’t know how it happened. I don’t think anyone took a vote on it. It happened gradually over the last decade. I think it happened when the administrative staff became larger than the medical staff. In order to include everyone under the same umbrella, everyone became a provider.

The title of doctor, nurse, technician all disappeared, and we all became providers. All those patients in our waiting room suddenly became consumers or clients. My grandfather ran a grocery store and had a lot of customers, and my father was a lawyer and had a lot of clients. None of those customers or clients would come to see me as their doctor with their illnesses today if I were a provider. The use of the terminology of “providers” and “customers” lowers all health care staff to the lowest common denominator and demeans the concerns of my patients.

I am not sure when it occurred. I don’t know how it happened. I don’t think anyone took a vote on it. It happened gradually over the last decade. I think it happened when the administrative staff became larger than the medical staff. In order to include everyone under the same umbrella, everyone became a provider.

The title of doctor, nurse, technician all disappeared, and we all became providers. All those patients in our waiting room suddenly became consumers or clients. My grandfather ran a grocery store and had a lot of customers, and my father was a lawyer and had a lot of clients. None of those customers or clients would come to see me as their doctor with their illnesses today if I were a provider. The use of the terminology of “providers” and “customers” lowers all health care staff to the lowest common denominator and demeans the concerns of my patients.

I am not sure when it occurred. I don’t know how it happened. I don’t think anyone took a vote on it. It happened gradually over the last decade. I think it happened when the administrative staff became larger than the medical staff. In order to include everyone under the same umbrella, everyone became a provider.

The title of doctor, nurse, technician all disappeared, and we all became providers. All those patients in our waiting room suddenly became consumers or clients. My grandfather ran a grocery store and had a lot of customers, and my father was a lawyer and had a lot of clients. None of those customers or clients would come to see me as their doctor with their illnesses today if I were a provider. The use of the terminology of “providers” and “customers” lowers all health care staff to the lowest common denominator and demeans the concerns of my patients.

NEW YORK – Recent discoveries regarding the relationship between alcohol consumption and neuroinflammation suggest a possible role for adjunctive treatments and supplements in addiction treatment, according to Shram Shukla, MD.

For example, a qualitative review of the literature over the past 2-3 years showed that the “neuroinflammatory process in and of itself drives epigenetic changes, which ultimately upregulate neuroinflammation of the brain,” according to Dr. Shukla of Walter Reed National Military Medical Center, Bethesda, Md., who reported the findings in a poster at the annual meeting of the American Psychiatric Association.

In this video interview, he explained that this finding is important because “neuroinflammation leads to neurotoxicity, which leads to neuronal degeneration.”

“As we know, with patients who chronically abuse alcohol, they do have a level of cortical degeneration that we often see on imaging, so there is, perhaps, a role that this may play in that,” he added.

Dr. Shukla said he also found that the neuroinflammatory process, when it drives the epigenetic changes, affects the amygdala, which is known as a “high stress part of the brain.”

“What we found in animal models so far is that if we can impact where that epigenetic change occurs, we can prevent the anxiogenic behaviors we often see in alcohol withdrawal and abstinence; we associate that, in humans, to be the high-stress state we often see in patients when they ... are withdrawing from alcohol.”

This raised questions about whether certain medications and supplements, including vitamin C, pioglitazone, infliximab, and omega-3 fatty acids, could be of benefit, and it was shown that these do affect neuroinflammation and stop neurotoxicity from occurring – and also, in turn, prevent the epigenetic changes, he said.

The take-away is that there may be ways to augment what already is being done (using naltrexone, which works on the reward pathway, for example) to help patients with addiction.

“Now we have something, potentially ... that can do some of the ancillary stuff, working on the withdrawal effects, helping with the behavioral response that we see in patients that are suffering from addiction,” he said.

Dr. Shukla reported having no disclosures.

[email protected]

SOURCE: Shukla S et al. APA Poster Session 4, Poster 3.

NEW YORK – Recent discoveries regarding the relationship between alcohol consumption and neuroinflammation suggest a possible role for adjunctive treatments and supplements in addiction treatment, according to Shram Shukla, MD.

For example, a qualitative review of the literature over the past 2-3 years showed that the “neuroinflammatory process in and of itself drives epigenetic changes, which ultimately upregulate neuroinflammation of the brain,” according to Dr. Shukla of Walter Reed National Military Medical Center, Bethesda, Md., who reported the findings in a poster at the annual meeting of the American Psychiatric Association.

In this video interview, he explained that this finding is important because “neuroinflammation leads to neurotoxicity, which leads to neuronal degeneration.”

“As we know, with patients who chronically abuse alcohol, they do have a level of cortical degeneration that we often see on imaging, so there is, perhaps, a role that this may play in that,” he added.

Dr. Shukla said he also found that the neuroinflammatory process, when it drives the epigenetic changes, affects the amygdala, which is known as a “high stress part of the brain.”

“What we found in animal models so far is that if we can impact where that epigenetic change occurs, we can prevent the anxiogenic behaviors we often see in alcohol withdrawal and abstinence; we associate that, in humans, to be the high-stress state we often see in patients when they ... are withdrawing from alcohol.”

This raised questions about whether certain medications and supplements, including vitamin C, pioglitazone, infliximab, and omega-3 fatty acids, could be of benefit, and it was shown that these do affect neuroinflammation and stop neurotoxicity from occurring – and also, in turn, prevent the epigenetic changes, he said.

The take-away is that there may be ways to augment what already is being done (using naltrexone, which works on the reward pathway, for example) to help patients with addiction.

“Now we have something, potentially ... that can do some of the ancillary stuff, working on the withdrawal effects, helping with the behavioral response that we see in patients that are suffering from addiction,” he said.

Dr. Shukla reported having no disclosures.

[email protected]

SOURCE: Shukla S et al. APA Poster Session 4, Poster 3.

NEW YORK – Recent discoveries regarding the relationship between alcohol consumption and neuroinflammation suggest a possible role for adjunctive treatments and supplements in addiction treatment, according to Shram Shukla, MD.

For example, a qualitative review of the literature over the past 2-3 years showed that the “neuroinflammatory process in and of itself drives epigenetic changes, which ultimately upregulate neuroinflammation of the brain,” according to Dr. Shukla of Walter Reed National Military Medical Center, Bethesda, Md., who reported the findings in a poster at the annual meeting of the American Psychiatric Association.

In this video interview, he explained that this finding is important because “neuroinflammation leads to neurotoxicity, which leads to neuronal degeneration.”

“As we know, with patients who chronically abuse alcohol, they do have a level of cortical degeneration that we often see on imaging, so there is, perhaps, a role that this may play in that,” he added.

Dr. Shukla said he also found that the neuroinflammatory process, when it drives the epigenetic changes, affects the amygdala, which is known as a “high stress part of the brain.”

“What we found in animal models so far is that if we can impact where that epigenetic change occurs, we can prevent the anxiogenic behaviors we often see in alcohol withdrawal and abstinence; we associate that, in humans, to be the high-stress state we often see in patients when they ... are withdrawing from alcohol.”

This raised questions about whether certain medications and supplements, including vitamin C, pioglitazone, infliximab, and omega-3 fatty acids, could be of benefit, and it was shown that these do affect neuroinflammation and stop neurotoxicity from occurring – and also, in turn, prevent the epigenetic changes, he said.

The take-away is that there may be ways to augment what already is being done (using naltrexone, which works on the reward pathway, for example) to help patients with addiction.

“Now we have something, potentially ... that can do some of the ancillary stuff, working on the withdrawal effects, helping with the behavioral response that we see in patients that are suffering from addiction,” he said.

Dr. Shukla reported having no disclosures.

[email protected]

SOURCE: Shukla S et al. APA Poster Session 4, Poster 3.

A novel vaccine may provide a breakthrough treatment option in colorectal and other cancers.

“We [researchers] at the Peter MacCallum Cancer Centre in Melbourne, Australia, have developed a new, DNA-based vaccine, which we call TetMYB, for the treatment of MYB-overexpressing cancers such as colorectal, adenoid cystic carcinoma, and breast cancer, to name a few,” Toan Pham, MD, of the Peter MacCallum Cancer Centre, said in a media briefing in advance of the annual Digestive Disease Week^® conference.

The immunotherapy approach described by Dr. Pham involves combining the TetMYB vaccine, which boosts the immune system, and an antibody, BGB-A317, that helps enhance the effectiveness of the vaccine.

luiscar/Thinkstock

[email protected]

A novel vaccine may provide a breakthrough treatment option in colorectal and other cancers.

“We [researchers] at the Peter MacCallum Cancer Centre in Melbourne, Australia, have developed a new, DNA-based vaccine, which we call TetMYB, for the treatment of MYB-overexpressing cancers such as colorectal, adenoid cystic carcinoma, and breast cancer, to name a few,” Toan Pham, MD, of the Peter MacCallum Cancer Centre, said in a media briefing in advance of the annual Digestive Disease Week^® conference.

The immunotherapy approach described by Dr. Pham involves combining the TetMYB vaccine, which boosts the immune system, and an antibody, BGB-A317, that helps enhance the effectiveness of the vaccine.

luiscar/Thinkstock

[email protected]

A novel vaccine may provide a breakthrough treatment option in colorectal and other cancers.

“We [researchers] at the Peter MacCallum Cancer Centre in Melbourne, Australia, have developed a new, DNA-based vaccine, which we call TetMYB, for the treatment of MYB-overexpressing cancers such as colorectal, adenoid cystic carcinoma, and breast cancer, to name a few,” Toan Pham, MD, of the Peter MacCallum Cancer Centre, said in a media briefing in advance of the annual Digestive Disease Week^® conference.

The immunotherapy approach described by Dr. Pham involves combining the TetMYB vaccine, which boosts the immune system, and an antibody, BGB-A317, that helps enhance the effectiveness of the vaccine.

luiscar/Thinkstock

[email protected]

As dermatologists, we possess a vast knowledge of the epidermis. Some patients may choose to use the epidermis as a canvas for their art in the form of tattoos; however, tattoos can complicate dermatology visits in a myriad of ways. From patients seeking tattoo removal (a complicated task even with the most advanced laser treatments) to those whose native skin is obscured by a tattoo during melanoma screening, it is no wonder that many dermatologists become frustrated at the very mention of the word tattoo.

Tattoos have a long and complicated history entrenched in class divisions, gender identity, and culture. Although its origins are not well documented, many researchers believe that tattooing began in Egypt as early as 4000 BCE.¹ From there, the practice spread east into South Asia and west to the British Isles and Scotland. The Iberians in the British Isles, the Picts in Scotland, the Gauls in Western Europe, and the Teutons in Germany all practiced tattooing, and the Romans were known to use tattooing to mark convicts and slaves.¹ By 787 AD, tattooing was prevalent enough to warrant an official ban by Pope Hadrian I at the Second Ecumenical Council of Nicaea.² The growing power of Christianity most likely contributed to the elimination of tattooing in the West, although many soldiers who fought in the Crusades received tattoos during their travels.³

Despite the long history of tattoos in both the East and West, Captain James Cook often is credited with discovering tattooing in the eighteenth century during his explorations in the Pacific.⁴ In Tahiti in 1769 and Hawaii in 1778, Cook encountered heavily tattooed populations who deposited dye into the skin by tapping sharpened instruments.³ These Polynesian tattoos, which were associated with healing and protective powers, often depicted genealogies and were composed of images of lines, stars, geometric designs, animals, and humans. Explorers in Polynesia who came after Cook noted that tattoo designs began to include rifles, cannons, and dates of chief’s deaths—an indication of the cultural exchange that occurred between Cook’s crew and the natives.³ The first tattooed peoples were displayed in the United States at the Centennial Exhibition in Philadelphia, Pennsylvania, in 1876.² Later, at the 1901 World’s Fair in Buffalo, New York, the first full “freak show” emerged, and tattooed “natives” were displayed.⁵ Since they were introduced in the West, tattoos have been associated with an element of the exotic in the United States.

Acknowledged by many to be the first professional tattooist in the United States, Martin Hildebrandt opened his shop in New York City, New York, in 1846.² Initially, only sailors and soldiers were tattooed, which contributed to the concept of the so-called “tattooed serviceman.”⁵ However, after the Spanish-American War, tattoos became a fad among the high society in Europe. Tattooing at this time was still performed through the ancient Polynesian tapping method, making it both time-consuming and expensive. Tattoos generally were always placed in a private location, leading to popular speculation at the time about whom in the aristocracy possessed a tattoo, with some even speculating that Queen Victoria may have had a tattoo.¹ However, this brief trend among the aristocracy came to an end when Samuel O’Reilly, an American tattoo artist, patented the first electric tattooing machine in 1891.⁶ His invention made tattooing faster, cheaper, and less painful, thereby making tattooing available to a much wider audience. In the United States, men in the military often were tattooed, especially during World Wars I and II, when patriotic themes and tattoos of important women in their lives (eg, the word Mom, the name of a sweetheart) became popular.

It is a popular belief that a tattoo renaissance occurred in the United States in the 1970s, sparked by an influx of Indonesian and Asian artistic styles. Today, tattoos are ubiquitous. A 2012 poll showed that 21% of adults in the United States have a tattoo.⁷ There are now 4 main types of tattoos: cosmetic (eg, permanent makeup), traumatic (eg, injury on asphalt), medical (eg, to mark radiation sites), and decorative—either amateur (often done by hand) or professional (done in tattoo parlors with electric tattooing needles).⁸

Laser Tattoo Removal

Today tattoos are easy and relatively cheap to get, and for most people they are not regarded as an important cultural milestone like they were in early Polynesian culture. As a result, dermatologists often may encounter patients seeking to have these permanent designs removed from their skin. Previously, tattoo removal was attempted using destructive processes such as scarification and cryotherapy and generally resulted in poor cosmetics outcomes. Today, lasers are at the forefront of tattoo removal. Traditional lasers use pulse durations in the nanosecond range, with newer generation lasers in the picosecond range delivering much shorter pulse durations, effectively delivering the same level of energy over less time. It is important to select the correct laser for optimal destruction of various tattoo ink colors (Table).^8,9

Controversy persists as to whether tattoo pigment destruction by lasers is caused by thermal or acoustic damage.¹⁰ It may be a combination of both, with rapid heating of the particles leading to a local shockwave as the energy collapses.¹¹ The goal of tattoo removal is to create smaller granules of pigment that can be taken up by the patient’s lymphatic system. The largest granule that can be taken up by the lymphatic system is 0.4 μm.¹⁰

In laser treatment of any skin condition, the laser energy is delivered in a pulse duration that should be less than the thermal relaxation time of the chromophores (water, melanin, hemoglobin, or tattoo pigment are the main targets within the skin).¹² Most tattoo chromophores are 30 nm to 300 nm, with a thermal relaxation time of less than 10 nanoseconds.^10,12 As the number of treatments progresses, laser settings should be adjusted for smaller ink particles. Patients should be warned about pain, side effects, and the need for multiple treatments. Common side effects of laser tattoo removal include purpura, pinpoint bleeding, erythema, edema, crusting, and blistering.⁸

After laser treatment, cytoplasmic water in the cell is converted into steam leading to cavitation of the lysosome, which presents as whitening of the skin. The whitening causes optical scatter, thereby preventing immediate retreatment of the area.¹¹ The R20 laser tattoo removal method discussed by Kossida et al,¹³ advises practitioners to wait 20 minutes between treatments to allow the air bubbles from the conversion of water to steam to disappear. Kossida et al¹³ demonstrated more effective removal in tattoos that were treated with this method compared to standard treatment. The recognition that trapped air bubbles delay multiple treatment cycles has led to the experimental use of perfluorodecalin, a fluorocarbon liquid capable of dissolving the air bubbles, for immediate retreatment.¹⁴ By dissolving the trapped air and eliminating the white color, multiple treatments can be completed during 1 session.

Risks of Laser Tattoo Removal

It is important to emphasize that there are potential risks associated with laser treatment for tattoo removal, many of which we are only just beginning to understand. Common side effects of laser treatment for tattoo removal include blisters, pain, bleeding, hyperpigmentation, or hypopigmentation; however, there also are rare potential risks. Tattoo ink can paradoxically darken when it contains metals such as titanium or zinc, as often is found in tan or white inks.¹⁵ The laser energy causes a shift of the metal from an oxidized to a reduced state, leading to a darker rather than lighter tattoo upon application of the laser. There also have been documented cases of intraprocedural anaphylaxis, delayed urticaria, as well as generalized eczematous reactions.^16-18 In these cases, the patients had never experienced any allergic symptoms prior to the laser tattoo removal procedure.

Additionally, patients with active allergy to the pigments used in tattoo ink provide a therapeutic dilemma, as laser treatment may potentially systematize the tattoo ink, leading to a more widespread allergic reaction. A case of a generalized eczematous reaction after carbon dioxide laser therapy in a patient with documented tattoo allergy has been reported.¹⁹ More research is needed to fully understand the nature of immediate as well as delayed hypersensitivity reactions associated with laser tattoo removal.

Final Thoughts

With thousands of years of established traditions, it is unlikely that tattooing will go away anytime soon. Fortunately, lasers are providing us with an effective and safe method of removal.

As dermatologists, we possess a vast knowledge of the epidermis. Some patients may choose to use the epidermis as a canvas for their art in the form of tattoos; however, tattoos can complicate dermatology visits in a myriad of ways. From patients seeking tattoo removal (a complicated task even with the most advanced laser treatments) to those whose native skin is obscured by a tattoo during melanoma screening, it is no wonder that many dermatologists become frustrated at the very mention of the word tattoo.

Tattoos have a long and complicated history entrenched in class divisions, gender identity, and culture. Although its origins are not well documented, many researchers believe that tattooing began in Egypt as early as 4000 BCE.¹ From there, the practice spread east into South Asia and west to the British Isles and Scotland. The Iberians in the British Isles, the Picts in Scotland, the Gauls in Western Europe, and the Teutons in Germany all practiced tattooing, and the Romans were known to use tattooing to mark convicts and slaves.¹ By 787 AD, tattooing was prevalent enough to warrant an official ban by Pope Hadrian I at the Second Ecumenical Council of Nicaea.² The growing power of Christianity most likely contributed to the elimination of tattooing in the West, although many soldiers who fought in the Crusades received tattoos during their travels.³

Despite the long history of tattoos in both the East and West, Captain James Cook often is credited with discovering tattooing in the eighteenth century during his explorations in the Pacific.⁴ In Tahiti in 1769 and Hawaii in 1778, Cook encountered heavily tattooed populations who deposited dye into the skin by tapping sharpened instruments.³ These Polynesian tattoos, which were associated with healing and protective powers, often depicted genealogies and were composed of images of lines, stars, geometric designs, animals, and humans. Explorers in Polynesia who came after Cook noted that tattoo designs began to include rifles, cannons, and dates of chief’s deaths—an indication of the cultural exchange that occurred between Cook’s crew and the natives.³ The first tattooed peoples were displayed in the United States at the Centennial Exhibition in Philadelphia, Pennsylvania, in 1876.² Later, at the 1901 World’s Fair in Buffalo, New York, the first full “freak show” emerged, and tattooed “natives” were displayed.⁵ Since they were introduced in the West, tattoos have been associated with an element of the exotic in the United States.

Acknowledged by many to be the first professional tattooist in the United States, Martin Hildebrandt opened his shop in New York City, New York, in 1846.² Initially, only sailors and soldiers were tattooed, which contributed to the concept of the so-called “tattooed serviceman.”⁵ However, after the Spanish-American War, tattoos became a fad among the high society in Europe. Tattooing at this time was still performed through the ancient Polynesian tapping method, making it both time-consuming and expensive. Tattoos generally were always placed in a private location, leading to popular speculation at the time about whom in the aristocracy possessed a tattoo, with some even speculating that Queen Victoria may have had a tattoo.¹ However, this brief trend among the aristocracy came to an end when Samuel O’Reilly, an American tattoo artist, patented the first electric tattooing machine in 1891.⁶ His invention made tattooing faster, cheaper, and less painful, thereby making tattooing available to a much wider audience. In the United States, men in the military often were tattooed, especially during World Wars I and II, when patriotic themes and tattoos of important women in their lives (eg, the word Mom, the name of a sweetheart) became popular.

It is a popular belief that a tattoo renaissance occurred in the United States in the 1970s, sparked by an influx of Indonesian and Asian artistic styles. Today, tattoos are ubiquitous. A 2012 poll showed that 21% of adults in the United States have a tattoo.⁷ There are now 4 main types of tattoos: cosmetic (eg, permanent makeup), traumatic (eg, injury on asphalt), medical (eg, to mark radiation sites), and decorative—either amateur (often done by hand) or professional (done in tattoo parlors with electric tattooing needles).⁸

Laser Tattoo Removal

Today tattoos are easy and relatively cheap to get, and for most people they are not regarded as an important cultural milestone like they were in early Polynesian culture. As a result, dermatologists often may encounter patients seeking to have these permanent designs removed from their skin. Previously, tattoo removal was attempted using destructive processes such as scarification and cryotherapy and generally resulted in poor cosmetics outcomes. Today, lasers are at the forefront of tattoo removal. Traditional lasers use pulse durations in the nanosecond range, with newer generation lasers in the picosecond range delivering much shorter pulse durations, effectively delivering the same level of energy over less time. It is important to select the correct laser for optimal destruction of various tattoo ink colors (Table).^8,9

Controversy persists as to whether tattoo pigment destruction by lasers is caused by thermal or acoustic damage.¹⁰ It may be a combination of both, with rapid heating of the particles leading to a local shockwave as the energy collapses.¹¹ The goal of tattoo removal is to create smaller granules of pigment that can be taken up by the patient’s lymphatic system. The largest granule that can be taken up by the lymphatic system is 0.4 μm.¹⁰

In laser treatment of any skin condition, the laser energy is delivered in a pulse duration that should be less than the thermal relaxation time of the chromophores (water, melanin, hemoglobin, or tattoo pigment are the main targets within the skin).¹² Most tattoo chromophores are 30 nm to 300 nm, with a thermal relaxation time of less than 10 nanoseconds.^10,12 As the number of treatments progresses, laser settings should be adjusted for smaller ink particles. Patients should be warned about pain, side effects, and the need for multiple treatments. Common side effects of laser tattoo removal include purpura, pinpoint bleeding, erythema, edema, crusting, and blistering.⁸

After laser treatment, cytoplasmic water in the cell is converted into steam leading to cavitation of the lysosome, which presents as whitening of the skin. The whitening causes optical scatter, thereby preventing immediate retreatment of the area.¹¹ The R20 laser tattoo removal method discussed by Kossida et al,¹³ advises practitioners to wait 20 minutes between treatments to allow the air bubbles from the conversion of water to steam to disappear. Kossida et al¹³ demonstrated more effective removal in tattoos that were treated with this method compared to standard treatment. The recognition that trapped air bubbles delay multiple treatment cycles has led to the experimental use of perfluorodecalin, a fluorocarbon liquid capable of dissolving the air bubbles, for immediate retreatment.¹⁴ By dissolving the trapped air and eliminating the white color, multiple treatments can be completed during 1 session.

Risks of Laser Tattoo Removal

It is important to emphasize that there are potential risks associated with laser treatment for tattoo removal, many of which we are only just beginning to understand. Common side effects of laser treatment for tattoo removal include blisters, pain, bleeding, hyperpigmentation, or hypopigmentation; however, there also are rare potential risks. Tattoo ink can paradoxically darken when it contains metals such as titanium or zinc, as often is found in tan or white inks.¹⁵ The laser energy causes a shift of the metal from an oxidized to a reduced state, leading to a darker rather than lighter tattoo upon application of the laser. There also have been documented cases of intraprocedural anaphylaxis, delayed urticaria, as well as generalized eczematous reactions.^16-18 In these cases, the patients had never experienced any allergic symptoms prior to the laser tattoo removal procedure.

Additionally, patients with active allergy to the pigments used in tattoo ink provide a therapeutic dilemma, as laser treatment may potentially systematize the tattoo ink, leading to a more widespread allergic reaction. A case of a generalized eczematous reaction after carbon dioxide laser therapy in a patient with documented tattoo allergy has been reported.¹⁹ More research is needed to fully understand the nature of immediate as well as delayed hypersensitivity reactions associated with laser tattoo removal.

Final Thoughts

With thousands of years of established traditions, it is unlikely that tattooing will go away anytime soon. Fortunately, lasers are providing us with an effective and safe method of removal.

As dermatologists, we possess a vast knowledge of the epidermis. Some patients may choose to use the epidermis as a canvas for their art in the form of tattoos; however, tattoos can complicate dermatology visits in a myriad of ways. From patients seeking tattoo removal (a complicated task even with the most advanced laser treatments) to those whose native skin is obscured by a tattoo during melanoma screening, it is no wonder that many dermatologists become frustrated at the very mention of the word tattoo.

Tattoos have a long and complicated history entrenched in class divisions, gender identity, and culture. Although its origins are not well documented, many researchers believe that tattooing began in Egypt as early as 4000 BCE.¹ From there, the practice spread east into South Asia and west to the British Isles and Scotland. The Iberians in the British Isles, the Picts in Scotland, the Gauls in Western Europe, and the Teutons in Germany all practiced tattooing, and the Romans were known to use tattooing to mark convicts and slaves.¹ By 787 AD, tattooing was prevalent enough to warrant an official ban by Pope Hadrian I at the Second Ecumenical Council of Nicaea.² The growing power of Christianity most likely contributed to the elimination of tattooing in the West, although many soldiers who fought in the Crusades received tattoos during their travels.³

Despite the long history of tattoos in both the East and West, Captain James Cook often is credited with discovering tattooing in the eighteenth century during his explorations in the Pacific.⁴ In Tahiti in 1769 and Hawaii in 1778, Cook encountered heavily tattooed populations who deposited dye into the skin by tapping sharpened instruments.³ These Polynesian tattoos, which were associated with healing and protective powers, often depicted genealogies and were composed of images of lines, stars, geometric designs, animals, and humans. Explorers in Polynesia who came after Cook noted that tattoo designs began to include rifles, cannons, and dates of chief’s deaths—an indication of the cultural exchange that occurred between Cook’s crew and the natives.³ The first tattooed peoples were displayed in the United States at the Centennial Exhibition in Philadelphia, Pennsylvania, in 1876.² Later, at the 1901 World’s Fair in Buffalo, New York, the first full “freak show” emerged, and tattooed “natives” were displayed.⁵ Since they were introduced in the West, tattoos have been associated with an element of the exotic in the United States.

Acknowledged by many to be the first professional tattooist in the United States, Martin Hildebrandt opened his shop in New York City, New York, in 1846.² Initially, only sailors and soldiers were tattooed, which contributed to the concept of the so-called “tattooed serviceman.”⁵ However, after the Spanish-American War, tattoos became a fad among the high society in Europe. Tattooing at this time was still performed through the ancient Polynesian tapping method, making it both time-consuming and expensive. Tattoos generally were always placed in a private location, leading to popular speculation at the time about whom in the aristocracy possessed a tattoo, with some even speculating that Queen Victoria may have had a tattoo.¹ However, this brief trend among the aristocracy came to an end when Samuel O’Reilly, an American tattoo artist, patented the first electric tattooing machine in 1891.⁶ His invention made tattooing faster, cheaper, and less painful, thereby making tattooing available to a much wider audience. In the United States, men in the military often were tattooed, especially during World Wars I and II, when patriotic themes and tattoos of important women in their lives (eg, the word Mom, the name of a sweetheart) became popular.

It is a popular belief that a tattoo renaissance occurred in the United States in the 1970s, sparked by an influx of Indonesian and Asian artistic styles. Today, tattoos are ubiquitous. A 2012 poll showed that 21% of adults in the United States have a tattoo.⁷ There are now 4 main types of tattoos: cosmetic (eg, permanent makeup), traumatic (eg, injury on asphalt), medical (eg, to mark radiation sites), and decorative—either amateur (often done by hand) or professional (done in tattoo parlors with electric tattooing needles).⁸

Laser Tattoo Removal

Today tattoos are easy and relatively cheap to get, and for most people they are not regarded as an important cultural milestone like they were in early Polynesian culture. As a result, dermatologists often may encounter patients seeking to have these permanent designs removed from their skin. Previously, tattoo removal was attempted using destructive processes such as scarification and cryotherapy and generally resulted in poor cosmetics outcomes. Today, lasers are at the forefront of tattoo removal. Traditional lasers use pulse durations in the nanosecond range, with newer generation lasers in the picosecond range delivering much shorter pulse durations, effectively delivering the same level of energy over less time. It is important to select the correct laser for optimal destruction of various tattoo ink colors (Table).^8,9

Controversy persists as to whether tattoo pigment destruction by lasers is caused by thermal or acoustic damage.¹⁰ It may be a combination of both, with rapid heating of the particles leading to a local shockwave as the energy collapses.¹¹ The goal of tattoo removal is to create smaller granules of pigment that can be taken up by the patient’s lymphatic system. The largest granule that can be taken up by the lymphatic system is 0.4 μm.¹⁰

In laser treatment of any skin condition, the laser energy is delivered in a pulse duration that should be less than the thermal relaxation time of the chromophores (water, melanin, hemoglobin, or tattoo pigment are the main targets within the skin).¹² Most tattoo chromophores are 30 nm to 300 nm, with a thermal relaxation time of less than 10 nanoseconds.^10,12 As the number of treatments progresses, laser settings should be adjusted for smaller ink particles. Patients should be warned about pain, side effects, and the need for multiple treatments. Common side effects of laser tattoo removal include purpura, pinpoint bleeding, erythema, edema, crusting, and blistering.⁸

After laser treatment, cytoplasmic water in the cell is converted into steam leading to cavitation of the lysosome, which presents as whitening of the skin. The whitening causes optical scatter, thereby preventing immediate retreatment of the area.¹¹ The R20 laser tattoo removal method discussed by Kossida et al,¹³ advises practitioners to wait 20 minutes between treatments to allow the air bubbles from the conversion of water to steam to disappear. Kossida et al¹³ demonstrated more effective removal in tattoos that were treated with this method compared to standard treatment. The recognition that trapped air bubbles delay multiple treatment cycles has led to the experimental use of perfluorodecalin, a fluorocarbon liquid capable of dissolving the air bubbles, for immediate retreatment.¹⁴ By dissolving the trapped air and eliminating the white color, multiple treatments can be completed during 1 session.

Risks of Laser Tattoo Removal

It is important to emphasize that there are potential risks associated with laser treatment for tattoo removal, many of which we are only just beginning to understand. Common side effects of laser treatment for tattoo removal include blisters, pain, bleeding, hyperpigmentation, or hypopigmentation; however, there also are rare potential risks. Tattoo ink can paradoxically darken when it contains metals such as titanium or zinc, as often is found in tan or white inks.¹⁵ The laser energy causes a shift of the metal from an oxidized to a reduced state, leading to a darker rather than lighter tattoo upon application of the laser. There also have been documented cases of intraprocedural anaphylaxis, delayed urticaria, as well as generalized eczematous reactions.^16-18 In these cases, the patients had never experienced any allergic symptoms prior to the laser tattoo removal procedure.

Additionally, patients with active allergy to the pigments used in tattoo ink provide a therapeutic dilemma, as laser treatment may potentially systematize the tattoo ink, leading to a more widespread allergic reaction. A case of a generalized eczematous reaction after carbon dioxide laser therapy in a patient with documented tattoo allergy has been reported.¹⁹ More research is needed to fully understand the nature of immediate as well as delayed hypersensitivity reactions associated with laser tattoo removal.

Final Thoughts

With thousands of years of established traditions, it is unlikely that tattooing will go away anytime soon. Fortunately, lasers are providing us with an effective and safe method of removal.

Where are they now? What have they been up to? CHEST’s Past Presidents each forged the way for the many successes of the American College of Chest Physicians, leading to enhanced patient care around the globe. Their outstanding leadership and vision are evidenced today in many of CHEST’s strategic initiatives. Let’s check in with Dr. D. Robert McCaffree, Master FCCP.

D. Robert McCaffree, MD, MSHA, Master FCCP

CHEST President 1997 - 1998

I received the chain of office (yes, there is an actual chain) from Dr. Bart Chernow in New Orleans during CHEST 1997. I remember this time as being a time of beginnings, challenges, and changes. Bart had been the stimulus for the CHEST Foundation and the form and function of this foundation was being developed. The women’s caucus (probably not the official name) was becoming more organized and more of a force under the leadership of Dr. Diane Stover and Dr. Deborah Shure and others, and the Woman, Girls, Tobacco, and Lung Cancer educational program was being refined. It was this program that got my wife, Mary Anne, involved with the CHEST, and she became a Fellow (FCCP). The American College of Chest Physicians was in the midst of the national tobacco settlement efforts at this time. Our involvement began when Mike Moore, Attorney-General of Mississippi, filed the first suit against the tobacco industry in 1994. Under the stimulus of Dr. John Studdard, our current President, the college was the only medical organization to file an amicus curiae brief supporting this, thus thrusting us into the midst of the tobacco settlement debates and in a leadership position. During the time I was President-elect and President, I was fortunate to represent us both in the ENACT Coalition (composed of national health groups, such as the American Cancer Society), as well as on the Koop-Kessler Congressional Advisory Committee. I also testified before Congress on the tobacco issues and met at the White House with DHHS Secretary Donna Shalala. On a different front, our international activities were not as developed as now, but we did make two memorable trips to India. Many thanks to Dr. Kay Guntupalli for helping make those trips so memorable. After this absolutely wonderful year, I passed the chain to Dr. Allen Goldberg in Toronto.

Where are they now? What have they been up to? CHEST’s Past Presidents each forged the way for the many successes of the American College of Chest Physicians, leading to enhanced patient care around the globe. Their outstanding leadership and vision are evidenced today in many of CHEST’s strategic initiatives. Let’s check in with Dr. D. Robert McCaffree, Master FCCP.

D. Robert McCaffree, MD, MSHA, Master FCCP

CHEST President 1997 - 1998

I received the chain of office (yes, there is an actual chain) from Dr. Bart Chernow in New Orleans during CHEST 1997. I remember this time as being a time of beginnings, challenges, and changes. Bart had been the stimulus for the CHEST Foundation and the form and function of this foundation was being developed. The women’s caucus (probably not the official name) was becoming more organized and more of a force under the leadership of Dr. Diane Stover and Dr. Deborah Shure and others, and the Woman, Girls, Tobacco, and Lung Cancer educational program was being refined. It was this program that got my wife, Mary Anne, involved with the CHEST, and she became a Fellow (FCCP). The American College of Chest Physicians was in the midst of the national tobacco settlement efforts at this time. Our involvement began when Mike Moore, Attorney-General of Mississippi, filed the first suit against the tobacco industry in 1994. Under the stimulus of Dr. John Studdard, our current President, the college was the only medical organization to file an amicus curiae brief supporting this, thus thrusting us into the midst of the tobacco settlement debates and in a leadership position. During the time I was President-elect and President, I was fortunate to represent us both in the ENACT Coalition (composed of national health groups, such as the American Cancer Society), as well as on the Koop-Kessler Congressional Advisory Committee. I also testified before Congress on the tobacco issues and met at the White House with DHHS Secretary Donna Shalala. On a different front, our international activities were not as developed as now, but we did make two memorable trips to India. Many thanks to Dr. Kay Guntupalli for helping make those trips so memorable. After this absolutely wonderful year, I passed the chain to Dr. Allen Goldberg in Toronto.

Where are they now? What have they been up to? CHEST’s Past Presidents each forged the way for the many successes of the American College of Chest Physicians, leading to enhanced patient care around the globe. Their outstanding leadership and vision are evidenced today in many of CHEST’s strategic initiatives. Let’s check in with Dr. D. Robert McCaffree, Master FCCP.

D. Robert McCaffree, MD, MSHA, Master FCCP

CHEST President 1997 - 1998

I received the chain of office (yes, there is an actual chain) from Dr. Bart Chernow in New Orleans during CHEST 1997. I remember this time as being a time of beginnings, challenges, and changes. Bart had been the stimulus for the CHEST Foundation and the form and function of this foundation was being developed. The women’s caucus (probably not the official name) was becoming more organized and more of a force under the leadership of Dr. Diane Stover and Dr. Deborah Shure and others, and the Woman, Girls, Tobacco, and Lung Cancer educational program was being refined. It was this program that got my wife, Mary Anne, involved with the CHEST, and she became a Fellow (FCCP). The American College of Chest Physicians was in the midst of the national tobacco settlement efforts at this time. Our involvement began when Mike Moore, Attorney-General of Mississippi, filed the first suit against the tobacco industry in 1994. Under the stimulus of Dr. John Studdard, our current President, the college was the only medical organization to file an amicus curiae brief supporting this, thus thrusting us into the midst of the tobacco settlement debates and in a leadership position. During the time I was President-elect and President, I was fortunate to represent us both in the ENACT Coalition (composed of national health groups, such as the American Cancer Society), as well as on the Koop-Kessler Congressional Advisory Committee. I also testified before Congress on the tobacco issues and met at the White House with DHHS Secretary Donna Shalala. On a different front, our international activities were not as developed as now, but we did make two memorable trips to India. Many thanks to Dr. Kay Guntupalli for helping make those trips so memorable. After this absolutely wonderful year, I passed the chain to Dr. Allen Goldberg in Toronto.

After discharge from the hospital, patients have a significantly elevated risk for adverse events, including emergency department use, hospital readmission, and death. More than 1 in 3 patients discharged from the hospital require acute care in the month after hospital discharge, and more than 1 in 6 require readmission, with readmission diagnoses frequently differing from those of the preceding hospitalization.^1-4 This heightened susceptibility to adverse events persists beyond 30 days but levels off by 7 weeks after discharge, suggesting that the period of increased risk is transient and dynamic.⁵

The term posthospital syndrome (PHS) describes this period of vulnerability to major adverse events following hospitalization.⁶ In addition to increased risk for readmission and mortality, patients in this period often show evidence of generalized dysfunction with new cognitive impairment, mobility disability, or functional decline.^7-12 To date, the etiology of this vulnerability is neither well understood nor effectively addressed by transitional care interventions.¹³

One hypothesis to explain PHS is that stressors associated with the experience of hospitalization contribute to transient multisystem dysfunction that induces susceptibility to a broad range of medical maladies. These stressors include frequent sleep disruption, noxious sounds, painful stimuli, mobility restrictions, and poor nutrition.¹² The stress hypothesis as a cause of PHS is therefore based, in large part, on evidence about allostasis and the deleterious effects of allostatic overload.

Allostasis defines a system functioning within normal stress-response parameters to promote adaptation and survival.¹⁴ In allostasis, the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic and parasympathetic branches of the autonomic nervous system (ANS) exist in homeostatic balance and respond to environmental stimuli within a range of healthy physiologic parameters. The hallmark of a system in allostasis is the ability to rapidly activate, then successfully deactivate, a stress response once the stressor (ie, threat) has resolved.^14,15 To promote survival and potentiate “fight or flight” mechanisms, an appropriate stress response necessarily impacts multiple physiologic systems that result in hemodynamic augmentation and gluconeogenesis to support the anticipated action of large muscle groups, heightened vigilance and memory capabilities to improve rapid decision-making, and enhancement of innate and adaptive immune capabilities to prepare for wound repair and infection defense.^14-16 The stress response is subsequently terminated by negative feedback mechanisms of glucocorticoids as well as a shift of the ANS from sympathetic to parasympathetic tone.^17,18

Extended or repetitive stress exposure, however, leads to dysregulation of allostatic mechanisms responsible for stress adaptation and hinders an efficient and effective stress response. After extended stress exposure, baseline (ie, resting) HPA activity resets, causing a disruption of normal diurnal cortisol rhythm and an increase in total cortisol concentration. Moreover, in response to stress, HPA and ANS system excitation becomes impaired, and negative feedback properties are undermined.^14,15 This maladaptive state, known as allostatic overload, disrupts the finely tuned mechanisms that are the foundation of mind-body balance and yields pathophysiologic consequences to multiple organ systems. Downstream ramifications of allostatic overload include cognitive deterioration, cardiovascular and immune system dysfunction, and functional decline.^14,15,19

Although a stress response is an expected and necessary aspect of acute illness that promotes survival, the central thesis of this work is that additional environmental and social stressors inherent in hospitalization may unnecessarily compound stress and increase the risk of HPA axis dysfunction, allostatic overload, and subsequent multisystem dysfunction, predisposing individuals to adverse outcomes after hospital discharge. Based on data from both human subjects and animal models, we present a possible pathophysiologic mechanism for the postdischarge vulnerability of PHS, encourage critical contemplation of traditional hospitalization, and suggest interventions that might improve outcomes.

Posthospital syndrome (PHS) describes a transient period of vulnerability after hospitalization during which patients are at elevated risk for adverse events from a broad range of conditions. In support of this characterization, epidemiologic data have demonstrated high rates of adverse outcomes following hospitalization. For example, data have shown that more than 1 in 6 older adults is readmitted to the hospital within 30 days of discharge.²⁰ Death is also common in this first month, during which rates of postdischarge mortality may exceed initial inpatient mortality.^21,22 Elevated vulnerability after hospitalization is not restricted to older adults, as readmission risk among younger patients 18 to 64 years of age may be even higher for selected conditions, such as heart failure.^3,23

Vulnerability after hospitalization is broad. In patients over age 65 initially admitted for heart failure or acute myocardial infarction, only 35% and 10% of readmissions are for recurrent heart failure or reinfarction, respectively.¹ Nearly half of readmissions are for noncardiovascular causes.¹ Similarly, following hospitalization for pneumonia, more than 60 percent of readmissions are for nonpulmonary etiologies. Moreover, the risk for all these causes of readmission is much higher than baseline risk, indicating an extended period of lack of resilience to many types of illness.²⁴ These patterns of broad susceptibility also extend to younger adults hospitalized with common medical conditions.³

Accumulating evidence suggests that hospitalized patients face functional decline, debility, and risk for adverse events despite resolution of the presenting illness, implying perhaps that the hospital environment itself is hazardous to patients’ health. In 1993, Creditor hypothesized that the “hazards of hospitalization,” including enforced bed-rest, sensory deprivation, social isolation, and malnutrition lead to a “cascade of dependency” in which a collection of small insults to multiple organ systems precipitates loss of function and debility despite cure or resolution of presenting illness.¹² Covinsky (2011) later defined hospitalization-associated disability as an iatrogenic hospital-related “disorder” characterized by new impairments in abilities to perform basic activities of daily living such as bathing, feeding, toileting, dressing, transferring, and walking at the time of hospital discharge.¹¹ Others have described a postintensive-care syndrome (PICS),²⁵ characterized by cognitive, psychiatric, and physical impairments acquired during hospitalization for critical illness that persist postdischarge and increase the long-term risk for adverse outcomes, including elevated mortality rates,^26,27 readmission rates,²⁸ and physical disabilities.²⁹ Similar to the “hazards of hospitalization,” PICS is thought to be related to common experiences of ICU stays, including mobility restriction, sensory deprivation, sleep disruption, sedation, malnutrition, and polypharmacy.^30-33

Taken together, these data suggest that adverse health consequences attributable to hospitalization extend across the spectrum of age, presenting disease severity, and hospital treatment location. As detailed below, the PHS hypothesis is rooted in a mechanistic understanding of the role of exogenous stressors in producing physiologic dysregulation and subsequent adverse health effects across multiple organ systems.

Nature of Stress in the Hospital

Compounding the stress of acute illness, hospitalized patients are routinely and repetitively exposed to a wide variety of environmental stressors that may have downstream adverse consequences (Table 1). In the absence of overt clinical manifestations of harm, the possible subclinical physiologic dysfunction generated by the following stress exposures may increase patients’ susceptibility to the manifestations of PHS.

Sleep Disruption

Sleep disruptions trigger potent stress responses,^34,35 yet they are common occurrences during hospitalization. In surveys, about half of patients report poor sleep quality during hospitalization that persists for many months after discharge.³⁶ In a simulated hospital setting, test subjects exposed to typical hospital sounds (paging system, machine alarms, etc.) experienced significant sleep-wake cycle abnormalities.³⁷ Although no work has yet focused specifically on the physiologic consequences of sleep disruption and stress in hospitalized patients, in healthy humans, mild sleep disruption has clear effects on allostasis by disrupting HPA activity, raising cortisol levels, diminishing parasympathetic tone, and impairing cognitive performance.^{18,34,35,38,39}

Malnourishment

Malnourishment in hospitalized patients is common, with one-fifth of hospitalized patients receiving nothing per mouth or clear liquid diets for more than 3 continuous days,⁴⁰ and one-fifth of hospitalized elderly patients receiving less than half of their calculated nutrition requirements.⁴¹ Although the relationship between food restriction, cortisol levels, and postdischarge outcomes has not been fully explored, in healthy humans, meal anticipation, meal withdrawal (withholding an expected meal), and self-reported dietary restraint are known to generate stress responses.^42,43 Furthermore, malnourishment during hospitalization is associated with increased 90-day and 1-year mortality after discharge,⁴⁴ adding malnourishment to the list of plausible components of hospital-related stress.

Mobility Restriction

Physical activity counterbalances stress responses and minimizes downstream consequences of allostatic load,¹⁵ yet mobility limitations via physical and chemical restraints are common in hospitalized patients, particularly among the elderly.^45-47 Many patients are tethered to devices that make ambulation hazardous, such as urinary catheters and infusion pumps. Even without physical or chemical restraints or a limited mobility order, patients may be hesitant to leave the room so as not to miss transport to a diagnostic study or an unscheduled physician’s visit. Indeed, mobility limitations of hospitalized patients increase the risk for adverse events after discharge, while interventions designed to encourage mobility are associated with improved postdischarge outcomes.^47,48

Other Stressors

Other hospital-related aversive stimuli are less commonly quantified, but clearly exist. According to surveys of hospitalized patients, sources of emotional stress include social isolation; loss of autonomy and privacy; fear of serious illness; lack of control over activities of daily living; lack of clear communication between treatment team and patients; and death of a patient roommate.^49,50 Furthermore, consider the physical discomfort and emotional distress of patients with urinary incontinence awaiting assistance for a diaper or bedding change or the pain of repetitive blood draws or other invasive testing. Although individualized, the subjective discomfort and emotional distress associated with these experiences undoubtedly contribute to the stress of hospitalization.

Animal Models of Stress

Laboratory techniques reminiscent of the numerous environmental stressors associated with hospitalization have been used to reliably trigger allostatic overload in healthy young animals.⁵¹ These techniques include sequential exposure to aversive stimuli, including food and water deprivation, continuous overnight illumination, paired housing with known and unknown cagemates, mobility restriction, soiled cage conditions, and continuous noise. All of these techniques have been shown to cause HPA axis and ANS dysfunction, allostatic overload, and subsequent stress-mediated consequences to multiple organ systems.^19,52-54 Given the remarkable similarity of these protocols to common experiences during hospitalization, animal models of stress may be useful in understanding the spectrum of maladaptive consequences experienced by patients within the hospital (Figure 1).

These animal models of stress have resulted in a number of instructive findings. For example, in rodents, extended stress exposure induces structural and functional remodeling of neuronal networks that precipitate learning and memory, working memory, and attention impairments.^55-57 These exposures also result in cardiovascular abnormalities, including dyslipidemia, progressive atherosclerosis,^58,59 and enhanced inflammatory cytokine expression,⁶⁰ all of which increase both atherosclerotic burden and susceptibility to plaque rupture, leading to elevated risk for major cardiovascular adverse events. Moreover, these extended stress exposures in animals increase susceptibility to both bacterial and viral infections and increase their severity.^16,61 This outcome appears to be driven by a stress-induced elevation of glucocorticoid levels, decreased leukocyte proliferation, altered leukocyte trafficking, and a transition to a proinflammatory cytokine environment.^{16, 61} Allostatic overload has also been shown to contribute to metabolic dysregulation involving insulin resistance, persistence of hyperglycemia, dyslipidemia, catabolism of lean muscle, and visceral adipose tissue deposition.^62-64 In addition to cardiovascular, immune, and metabolic consequences of allostatic overload, the spectrum of physiologic dysfunction in animal models is broad and includes mood disorder symptoms,⁶⁵ intestinal barrier abnormalities,⁶⁶ airway reactivity exacerbation,⁶⁷ and enhanced tumor growth.⁶⁸

Although the majority of this research highlights the multisystem effects of variable stress exposure in healthy animals, preliminary evidence suggests that aged or diseased animals subjected to additional stressors display a heightened inflammatory cytokine response that contributes to exaggerated sickness behavior and greater and prolonged cognitive deficits.⁶⁹ Future studies exploring the consequences of extended stress exposure in animals with existing disease or debility may therefore more closely simulate the experience of hospitalized patients and perhaps further our understanding of PHS.

Hospitalized Patients

While no intervention studies have examined the effects of potential hospital stressors on the development of allostatic overload, there is evidence from small studies that dysregulated stress responses during hospitalization are associated with adverse events. For example, high serum cortisol, catecholamine, and proinflammatory cytokine levels during hospitalization have individually been associated with the development of cognitive dysfunction,^70-72 increased risk of cardiovascular events such as myocardial infarction and stroke in the year following discharge,^73-76 and the development of wound infections after discharge.⁷⁷ Moreover, elevated plasma glucose during admission for myocardial infarction in patients with or without diabetes has been associated with greater in-hospital and 1-year mortality,⁷⁸ with a similar relationship seen between elevated plasma glucose and survival after admission for stroke⁷⁹ and pneumonia.⁸⁰ Furthermore, in addition to atherothrombosis, stress may contribute to the risk for venous thromboembolism,⁸¹ resulting in readmissions for deep vein thrombosis or pulmonary embolism posthospitalization. Although potentially surrogate markers of illness acuity, a handful of studies have shown that these stress biomarkers are actually only weakly correlated with,⁸² or independent of,^72,76 disease severity. As discussed in detail below, future studies utilizing a summative measure of multisystem physiologic dysfunction as opposed to individual biomarkers may more accurately reflect the cumulative stress effects of hospitalization and subsequent risk for adverse events.

Additional Considerations

Elderly patients, in particular, may have heightened susceptibility to the consequences of allostatic overload due to common geriatric issues such as multimorbidity and frailty. Patients with chronic diseases display both baseline HPA axis abnormalities as well as dysregulated stress responses and may therefore be more vulnerable to hospitalization-related stress. For example, when subjected to psychosocial stress, patients with chronic conditions such as diabetes, heart failure, or atherosclerosis demonstrate elevated cortisol levels, increased circulating markers of inflammation, as well as prolonged hemodynamic recovery after stress resolution compared with normal controls.^83-85 Additionally, frailty may affect an individual’s susceptibility to exogenous stress. Indeed, frailty identified on hospital admission increases the risk for adverse outcomes during hospitalization and postdischarge.⁸⁶ Although the specific etiology of this relationship is unclear, persons with frailty are known to have elevated levels of cortisol and other inflammatory markers,^87,88 which may contribute to adverse outcomes in the face of additional stressors.

A large body of evidence stretching from bench to bedside suggests that environmental stressors associated with hospitalization are toxic. Understanding PHS within the context of hospital-induced allostatic overload presents a unifying theory for the interrelated multisystem dysfunction and increased susceptibility to adverse events that patients experience after discharge (Figure 2). Furthermore, it defines a potential pathophysiological mechanism for the cognitive impairment, elevated cardiovascular risk, immune system dysfunction, metabolic derangements, and functional decline associated with PHS. Additionally, this theory highlights environmental interventions to limit PHS development and suggests mechanisms to promote stress resilience. Although it is difficult to disentangle the consequences of the endogenous stress triggered by an acute illness from the exogenous stressors related to hospitalization, it is likely that the 2 simultaneous exposures compound risk for stress system dysregulation and allostatic overload. Moreover, hospitalized patients with preexisting HPA axis dysfunction at baseline from chronic disease or advancing age may be even more susceptible to these adverse outcomes. If this hypothesis is true, a reduction in PHS would require mitigation of the modifiable environmental stressors encountered by patients during hospitalization. Directed efforts to diminish ambient noise, limit nighttime disruptions, thoughtfully plan procedures, consider ongoing nutritional status, and promote opportunities for patients to exert some control over their environment may diminish the burden of extrinsic stressors encountered by all patients in the hospital and improve outcomes after discharge.

Hospitals are increasingly recognizing the importance of improving patients’ experience of hospitalization by reducing exposure to potential toxicities. For example, many hospitals are now attempting to reduce sleep disturbances and sleep latency through reduced nighttime noise and light levels, fewer nighttime interruptions for vital signs checks and medication administration, and commonsensical interventions like massages, herbal teas, and warm milk prior to bedtime.⁸⁹ Likewise, intensive care units are targeting environmental and physical stressors with a multifaceted approach to decrease sedative use, promote healthy sleep cycles, and encourage exercise and ambulation even in those patients who are mechanically ventilated.³⁰ Another promising development has been the increase of Hospital at Home programs. In these programs, patients who meet the criteria for inpatient admission are instead comprehensively managed at home for their acute illness through a multidisciplinary effort between physicians, nurses, social workers, physical therapists, and others. Patients hospitalized at home report higher levels of satisfaction and have modest functional gains, improved health-related quality of life, and decreased risk of mortality at 6 months compared with hospitalized patients.^90,91 With some admitting diagnoses (eg, heart failure), hospitalization at home may be associated with decreased readmission risk.⁹² Although not yet investigated on a physiologic level, perhaps the benefits of hospital at home are partially due to the dramatic difference in exposure to environmental stressors.

A tool that quantifies hospital-associated stress may help health providers appreciate the experience of patients and better target interventions to aspects of their structure and process that contribute to allostatic overload. Importantly, allostatic overload cannot be identified by one biomarker of stress but instead requires evidence of dysregulation across inflammatory, neuroendocrine, hormonal, and cardiometabolic systems. Future studies to address the burden of stress faced by hospitalized patients should consider a summative measure of multisystem dysregulation as opposed to isolated assessments of individual biomarkers. Allostatic load has previously been operationalized as the summation of a variety of hemodynamic, hormonal, and metabolic factors, including blood pressure, lipid profile, glycosylated hemoglobin, cortisol, catecholamine levels, and inflammatory markers.⁹³ To develop a hospital-associated allostatic load index, models should ideally be adjusted for acute illness severity, patient-reported stress, and capacity for stress resilience. This tool could then be used to quantify hospitalization-related allostatic load and identify those at greatest risk for adverse events after discharge, as well as measure the effectiveness of strategic environmental interventions (Table 2). A natural first experiment may be a comparison of the allostatic load of hospitalized patients versus those hospitalized at home.

After discharge from the hospital, patients have a significantly elevated risk for adverse events, including emergency department use, hospital readmission, and death. More than 1 in 3 patients discharged from the hospital require acute care in the month after hospital discharge, and more than 1 in 6 require readmission, with readmission diagnoses frequently differing from those of the preceding hospitalization.^1-4 This heightened susceptibility to adverse events persists beyond 30 days but levels off by 7 weeks after discharge, suggesting that the period of increased risk is transient and dynamic.⁵

The term posthospital syndrome (PHS) describes this period of vulnerability to major adverse events following hospitalization.⁶ In addition to increased risk for readmission and mortality, patients in this period often show evidence of generalized dysfunction with new cognitive impairment, mobility disability, or functional decline.^7-12 To date, the etiology of this vulnerability is neither well understood nor effectively addressed by transitional care interventions.¹³

One hypothesis to explain PHS is that stressors associated with the experience of hospitalization contribute to transient multisystem dysfunction that induces susceptibility to a broad range of medical maladies. These stressors include frequent sleep disruption, noxious sounds, painful stimuli, mobility restrictions, and poor nutrition.¹² The stress hypothesis as a cause of PHS is therefore based, in large part, on evidence about allostasis and the deleterious effects of allostatic overload.

Allostasis defines a system functioning within normal stress-response parameters to promote adaptation and survival.¹⁴ In allostasis, the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic and parasympathetic branches of the autonomic nervous system (ANS) exist in homeostatic balance and respond to environmental stimuli within a range of healthy physiologic parameters. The hallmark of a system in allostasis is the ability to rapidly activate, then successfully deactivate, a stress response once the stressor (ie, threat) has resolved.^14,15 To promote survival and potentiate “fight or flight” mechanisms, an appropriate stress response necessarily impacts multiple physiologic systems that result in hemodynamic augmentation and gluconeogenesis to support the anticipated action of large muscle groups, heightened vigilance and memory capabilities to improve rapid decision-making, and enhancement of innate and adaptive immune capabilities to prepare for wound repair and infection defense.^14-16 The stress response is subsequently terminated by negative feedback mechanisms of glucocorticoids as well as a shift of the ANS from sympathetic to parasympathetic tone.^17,18

Extended or repetitive stress exposure, however, leads to dysregulation of allostatic mechanisms responsible for stress adaptation and hinders an efficient and effective stress response. After extended stress exposure, baseline (ie, resting) HPA activity resets, causing a disruption of normal diurnal cortisol rhythm and an increase in total cortisol concentration. Moreover, in response to stress, HPA and ANS system excitation becomes impaired, and negative feedback properties are undermined.^14,15 This maladaptive state, known as allostatic overload, disrupts the finely tuned mechanisms that are the foundation of mind-body balance and yields pathophysiologic consequences to multiple organ systems. Downstream ramifications of allostatic overload include cognitive deterioration, cardiovascular and immune system dysfunction, and functional decline.^14,15,19

Although a stress response is an expected and necessary aspect of acute illness that promotes survival, the central thesis of this work is that additional environmental and social stressors inherent in hospitalization may unnecessarily compound stress and increase the risk of HPA axis dysfunction, allostatic overload, and subsequent multisystem dysfunction, predisposing individuals to adverse outcomes after hospital discharge. Based on data from both human subjects and animal models, we present a possible pathophysiologic mechanism for the postdischarge vulnerability of PHS, encourage critical contemplation of traditional hospitalization, and suggest interventions that might improve outcomes.

Posthospital syndrome (PHS) describes a transient period of vulnerability after hospitalization during which patients are at elevated risk for adverse events from a broad range of conditions. In support of this characterization, epidemiologic data have demonstrated high rates of adverse outcomes following hospitalization. For example, data have shown that more than 1 in 6 older adults is readmitted to the hospital within 30 days of discharge.²⁰ Death is also common in this first month, during which rates of postdischarge mortality may exceed initial inpatient mortality.^21,22 Elevated vulnerability after hospitalization is not restricted to older adults, as readmission risk among younger patients 18 to 64 years of age may be even higher for selected conditions, such as heart failure.^3,23

Vulnerability after hospitalization is broad. In patients over age 65 initially admitted for heart failure or acute myocardial infarction, only 35% and 10% of readmissions are for recurrent heart failure or reinfarction, respectively.¹ Nearly half of readmissions are for noncardiovascular causes.¹ Similarly, following hospitalization for pneumonia, more than 60 percent of readmissions are for nonpulmonary etiologies. Moreover, the risk for all these causes of readmission is much higher than baseline risk, indicating an extended period of lack of resilience to many types of illness.²⁴ These patterns of broad susceptibility also extend to younger adults hospitalized with common medical conditions.³

Accumulating evidence suggests that hospitalized patients face functional decline, debility, and risk for adverse events despite resolution of the presenting illness, implying perhaps that the hospital environment itself is hazardous to patients’ health. In 1993, Creditor hypothesized that the “hazards of hospitalization,” including enforced bed-rest, sensory deprivation, social isolation, and malnutrition lead to a “cascade of dependency” in which a collection of small insults to multiple organ systems precipitates loss of function and debility despite cure or resolution of presenting illness.¹² Covinsky (2011) later defined hospitalization-associated disability as an iatrogenic hospital-related “disorder” characterized by new impairments in abilities to perform basic activities of daily living such as bathing, feeding, toileting, dressing, transferring, and walking at the time of hospital discharge.¹¹ Others have described a postintensive-care syndrome (PICS),²⁵ characterized by cognitive, psychiatric, and physical impairments acquired during hospitalization for critical illness that persist postdischarge and increase the long-term risk for adverse outcomes, including elevated mortality rates,^26,27 readmission rates,²⁸ and physical disabilities.²⁹ Similar to the “hazards of hospitalization,” PICS is thought to be related to common experiences of ICU stays, including mobility restriction, sensory deprivation, sleep disruption, sedation, malnutrition, and polypharmacy.^30-33

Taken together, these data suggest that adverse health consequences attributable to hospitalization extend across the spectrum of age, presenting disease severity, and hospital treatment location. As detailed below, the PHS hypothesis is rooted in a mechanistic understanding of the role of exogenous stressors in producing physiologic dysregulation and subsequent adverse health effects across multiple organ systems.

Nature of Stress in the Hospital

Compounding the stress of acute illness, hospitalized patients are routinely and repetitively exposed to a wide variety of environmental stressors that may have downstream adverse consequences (Table 1). In the absence of overt clinical manifestations of harm, the possible subclinical physiologic dysfunction generated by the following stress exposures may increase patients’ susceptibility to the manifestations of PHS.

Sleep Disruption

Sleep disruptions trigger potent stress responses,^34,35 yet they are common occurrences during hospitalization. In surveys, about half of patients report poor sleep quality during hospitalization that persists for many months after discharge.³⁶ In a simulated hospital setting, test subjects exposed to typical hospital sounds (paging system, machine alarms, etc.) experienced significant sleep-wake cycle abnormalities.³⁷ Although no work has yet focused specifically on the physiologic consequences of sleep disruption and stress in hospitalized patients, in healthy humans, mild sleep disruption has clear effects on allostasis by disrupting HPA activity, raising cortisol levels, diminishing parasympathetic tone, and impairing cognitive performance.^{18,34,35,38,39}

Malnourishment

Malnourishment in hospitalized patients is common, with one-fifth of hospitalized patients receiving nothing per mouth or clear liquid diets for more than 3 continuous days,⁴⁰ and one-fifth of hospitalized elderly patients receiving less than half of their calculated nutrition requirements.⁴¹ Although the relationship between food restriction, cortisol levels, and postdischarge outcomes has not been fully explored, in healthy humans, meal anticipation, meal withdrawal (withholding an expected meal), and self-reported dietary restraint are known to generate stress responses.^42,43 Furthermore, malnourishment during hospitalization is associated with increased 90-day and 1-year mortality after discharge,⁴⁴ adding malnourishment to the list of plausible components of hospital-related stress.

Mobility Restriction

Physical activity counterbalances stress responses and minimizes downstream consequences of allostatic load,¹⁵ yet mobility limitations via physical and chemical restraints are common in hospitalized patients, particularly among the elderly.^45-47 Many patients are tethered to devices that make ambulation hazardous, such as urinary catheters and infusion pumps. Even without physical or chemical restraints or a limited mobility order, patients may be hesitant to leave the room so as not to miss transport to a diagnostic study or an unscheduled physician’s visit. Indeed, mobility limitations of hospitalized patients increase the risk for adverse events after discharge, while interventions designed to encourage mobility are associated with improved postdischarge outcomes.^47,48

Other Stressors

Other hospital-related aversive stimuli are less commonly quantified, but clearly exist. According to surveys of hospitalized patients, sources of emotional stress include social isolation; loss of autonomy and privacy; fear of serious illness; lack of control over activities of daily living; lack of clear communication between treatment team and patients; and death of a patient roommate.^49,50 Furthermore, consider the physical discomfort and emotional distress of patients with urinary incontinence awaiting assistance for a diaper or bedding change or the pain of repetitive blood draws or other invasive testing. Although individualized, the subjective discomfort and emotional distress associated with these experiences undoubtedly contribute to the stress of hospitalization.

Animal Models of Stress

Laboratory techniques reminiscent of the numerous environmental stressors associated with hospitalization have been used to reliably trigger allostatic overload in healthy young animals.⁵¹ These techniques include sequential exposure to aversive stimuli, including food and water deprivation, continuous overnight illumination, paired housing with known and unknown cagemates, mobility restriction, soiled cage conditions, and continuous noise. All of these techniques have been shown to cause HPA axis and ANS dysfunction, allostatic overload, and subsequent stress-mediated consequences to multiple organ systems.^19,52-54 Given the remarkable similarity of these protocols to common experiences during hospitalization, animal models of stress may be useful in understanding the spectrum of maladaptive consequences experienced by patients within the hospital (Figure 1).

These animal models of stress have resulted in a number of instructive findings. For example, in rodents, extended stress exposure induces structural and functional remodeling of neuronal networks that precipitate learning and memory, working memory, and attention impairments.^55-57 These exposures also result in cardiovascular abnormalities, including dyslipidemia, progressive atherosclerosis,^58,59 and enhanced inflammatory cytokine expression,⁶⁰ all of which increase both atherosclerotic burden and susceptibility to plaque rupture, leading to elevated risk for major cardiovascular adverse events. Moreover, these extended stress exposures in animals increase susceptibility to both bacterial and viral infections and increase their severity.^16,61 This outcome appears to be driven by a stress-induced elevation of glucocorticoid levels, decreased leukocyte proliferation, altered leukocyte trafficking, and a transition to a proinflammatory cytokine environment.^{16, 61} Allostatic overload has also been shown to contribute to metabolic dysregulation involving insulin resistance, persistence of hyperglycemia, dyslipidemia, catabolism of lean muscle, and visceral adipose tissue deposition.^62-64 In addition to cardiovascular, immune, and metabolic consequences of allostatic overload, the spectrum of physiologic dysfunction in animal models is broad and includes mood disorder symptoms,⁶⁵ intestinal barrier abnormalities,⁶⁶ airway reactivity exacerbation,⁶⁷ and enhanced tumor growth.⁶⁸

Although the majority of this research highlights the multisystem effects of variable stress exposure in healthy animals, preliminary evidence suggests that aged or diseased animals subjected to additional stressors display a heightened inflammatory cytokine response that contributes to exaggerated sickness behavior and greater and prolonged cognitive deficits.⁶⁹ Future studies exploring the consequences of extended stress exposure in animals with existing disease or debility may therefore more closely simulate the experience of hospitalized patients and perhaps further our understanding of PHS.

Hospitalized Patients

While no intervention studies have examined the effects of potential hospital stressors on the development of allostatic overload, there is evidence from small studies that dysregulated stress responses during hospitalization are associated with adverse events. For example, high serum cortisol, catecholamine, and proinflammatory cytokine levels during hospitalization have individually been associated with the development of cognitive dysfunction,^70-72 increased risk of cardiovascular events such as myocardial infarction and stroke in the year following discharge,^73-76 and the development of wound infections after discharge.⁷⁷ Moreover, elevated plasma glucose during admission for myocardial infarction in patients with or without diabetes has been associated with greater in-hospital and 1-year mortality,⁷⁸ with a similar relationship seen between elevated plasma glucose and survival after admission for stroke⁷⁹ and pneumonia.⁸⁰ Furthermore, in addition to atherothrombosis, stress may contribute to the risk for venous thromboembolism,⁸¹ resulting in readmissions for deep vein thrombosis or pulmonary embolism posthospitalization. Although potentially surrogate markers of illness acuity, a handful of studies have shown that these stress biomarkers are actually only weakly correlated with,⁸² or independent of,^72,76 disease severity. As discussed in detail below, future studies utilizing a summative measure of multisystem physiologic dysfunction as opposed to individual biomarkers may more accurately reflect the cumulative stress effects of hospitalization and subsequent risk for adverse events.

Additional Considerations

Elderly patients, in particular, may have heightened susceptibility to the consequences of allostatic overload due to common geriatric issues such as multimorbidity and frailty. Patients with chronic diseases display both baseline HPA axis abnormalities as well as dysregulated stress responses and may therefore be more vulnerable to hospitalization-related stress. For example, when subjected to psychosocial stress, patients with chronic conditions such as diabetes, heart failure, or atherosclerosis demonstrate elevated cortisol levels, increased circulating markers of inflammation, as well as prolonged hemodynamic recovery after stress resolution compared with normal controls.^83-85 Additionally, frailty may affect an individual’s susceptibility to exogenous stress. Indeed, frailty identified on hospital admission increases the risk for adverse outcomes during hospitalization and postdischarge.⁸⁶ Although the specific etiology of this relationship is unclear, persons with frailty are known to have elevated levels of cortisol and other inflammatory markers,^87,88 which may contribute to adverse outcomes in the face of additional stressors.

A large body of evidence stretching from bench to bedside suggests that environmental stressors associated with hospitalization are toxic. Understanding PHS within the context of hospital-induced allostatic overload presents a unifying theory for the interrelated multisystem dysfunction and increased susceptibility to adverse events that patients experience after discharge (Figure 2). Furthermore, it defines a potential pathophysiological mechanism for the cognitive impairment, elevated cardiovascular risk, immune system dysfunction, metabolic derangements, and functional decline associated with PHS. Additionally, this theory highlights environmental interventions to limit PHS development and suggests mechanisms to promote stress resilience. Although it is difficult to disentangle the consequences of the endogenous stress triggered by an acute illness from the exogenous stressors related to hospitalization, it is likely that the 2 simultaneous exposures compound risk for stress system dysregulation and allostatic overload. Moreover, hospitalized patients with preexisting HPA axis dysfunction at baseline from chronic disease or advancing age may be even more susceptible to these adverse outcomes. If this hypothesis is true, a reduction in PHS would require mitigation of the modifiable environmental stressors encountered by patients during hospitalization. Directed efforts to diminish ambient noise, limit nighttime disruptions, thoughtfully plan procedures, consider ongoing nutritional status, and promote opportunities for patients to exert some control over their environment may diminish the burden of extrinsic stressors encountered by all patients in the hospital and improve outcomes after discharge.

Hospitals are increasingly recognizing the importance of improving patients’ experience of hospitalization by reducing exposure to potential toxicities. For example, many hospitals are now attempting to reduce sleep disturbances and sleep latency through reduced nighttime noise and light levels, fewer nighttime interruptions for vital signs checks and medication administration, and commonsensical interventions like massages, herbal teas, and warm milk prior to bedtime.⁸⁹ Likewise, intensive care units are targeting environmental and physical stressors with a multifaceted approach to decrease sedative use, promote healthy sleep cycles, and encourage exercise and ambulation even in those patients who are mechanically ventilated.³⁰ Another promising development has been the increase of Hospital at Home programs. In these programs, patients who meet the criteria for inpatient admission are instead comprehensively managed at home for their acute illness through a multidisciplinary effort between physicians, nurses, social workers, physical therapists, and others. Patients hospitalized at home report higher levels of satisfaction and have modest functional gains, improved health-related quality of life, and decreased risk of mortality at 6 months compared with hospitalized patients.^90,91 With some admitting diagnoses (eg, heart failure), hospitalization at home may be associated with decreased readmission risk.⁹² Although not yet investigated on a physiologic level, perhaps the benefits of hospital at home are partially due to the dramatic difference in exposure to environmental stressors.

A tool that quantifies hospital-associated stress may help health providers appreciate the experience of patients and better target interventions to aspects of their structure and process that contribute to allostatic overload. Importantly, allostatic overload cannot be identified by one biomarker of stress but instead requires evidence of dysregulation across inflammatory, neuroendocrine, hormonal, and cardiometabolic systems. Future studies to address the burden of stress faced by hospitalized patients should consider a summative measure of multisystem dysregulation as opposed to isolated assessments of individual biomarkers. Allostatic load has previously been operationalized as the summation of a variety of hemodynamic, hormonal, and metabolic factors, including blood pressure, lipid profile, glycosylated hemoglobin, cortisol, catecholamine levels, and inflammatory markers.⁹³ To develop a hospital-associated allostatic load index, models should ideally be adjusted for acute illness severity, patient-reported stress, and capacity for stress resilience. This tool could then be used to quantify hospitalization-related allostatic load and identify those at greatest risk for adverse events after discharge, as well as measure the effectiveness of strategic environmental interventions (Table 2). A natural first experiment may be a comparison of the allostatic load of hospitalized patients versus those hospitalized at home.

After discharge from the hospital, patients have a significantly elevated risk for adverse events, including emergency department use, hospital readmission, and death. More than 1 in 3 patients discharged from the hospital require acute care in the month after hospital discharge, and more than 1 in 6 require readmission, with readmission diagnoses frequently differing from those of the preceding hospitalization.^1-4 This heightened susceptibility to adverse events persists beyond 30 days but levels off by 7 weeks after discharge, suggesting that the period of increased risk is transient and dynamic.⁵

The term posthospital syndrome (PHS) describes this period of vulnerability to major adverse events following hospitalization.⁶ In addition to increased risk for readmission and mortality, patients in this period often show evidence of generalized dysfunction with new cognitive impairment, mobility disability, or functional decline.^7-12 To date, the etiology of this vulnerability is neither well understood nor effectively addressed by transitional care interventions.¹³

One hypothesis to explain PHS is that stressors associated with the experience of hospitalization contribute to transient multisystem dysfunction that induces susceptibility to a broad range of medical maladies. These stressors include frequent sleep disruption, noxious sounds, painful stimuli, mobility restrictions, and poor nutrition.¹² The stress hypothesis as a cause of PHS is therefore based, in large part, on evidence about allostasis and the deleterious effects of allostatic overload.

Allostasis defines a system functioning within normal stress-response parameters to promote adaptation and survival.¹⁴ In allostasis, the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic and parasympathetic branches of the autonomic nervous system (ANS) exist in homeostatic balance and respond to environmental stimuli within a range of healthy physiologic parameters. The hallmark of a system in allostasis is the ability to rapidly activate, then successfully deactivate, a stress response once the stressor (ie, threat) has resolved.^14,15 To promote survival and potentiate “fight or flight” mechanisms, an appropriate stress response necessarily impacts multiple physiologic systems that result in hemodynamic augmentation and gluconeogenesis to support the anticipated action of large muscle groups, heightened vigilance and memory capabilities to improve rapid decision-making, and enhancement of innate and adaptive immune capabilities to prepare for wound repair and infection defense.^14-16 The stress response is subsequently terminated by negative feedback mechanisms of glucocorticoids as well as a shift of the ANS from sympathetic to parasympathetic tone.^17,18

Extended or repetitive stress exposure, however, leads to dysregulation of allostatic mechanisms responsible for stress adaptation and hinders an efficient and effective stress response. After extended stress exposure, baseline (ie, resting) HPA activity resets, causing a disruption of normal diurnal cortisol rhythm and an increase in total cortisol concentration. Moreover, in response to stress, HPA and ANS system excitation becomes impaired, and negative feedback properties are undermined.^14,15 This maladaptive state, known as allostatic overload, disrupts the finely tuned mechanisms that are the foundation of mind-body balance and yields pathophysiologic consequences to multiple organ systems. Downstream ramifications of allostatic overload include cognitive deterioration, cardiovascular and immune system dysfunction, and functional decline.^14,15,19

Although a stress response is an expected and necessary aspect of acute illness that promotes survival, the central thesis of this work is that additional environmental and social stressors inherent in hospitalization may unnecessarily compound stress and increase the risk of HPA axis dysfunction, allostatic overload, and subsequent multisystem dysfunction, predisposing individuals to adverse outcomes after hospital discharge. Based on data from both human subjects and animal models, we present a possible pathophysiologic mechanism for the postdischarge vulnerability of PHS, encourage critical contemplation of traditional hospitalization, and suggest interventions that might improve outcomes.

Posthospital syndrome (PHS) describes a transient period of vulnerability after hospitalization during which patients are at elevated risk for adverse events from a broad range of conditions. In support of this characterization, epidemiologic data have demonstrated high rates of adverse outcomes following hospitalization. For example, data have shown that more than 1 in 6 older adults is readmitted to the hospital within 30 days of discharge.²⁰ Death is also common in this first month, during which rates of postdischarge mortality may exceed initial inpatient mortality.^21,22 Elevated vulnerability after hospitalization is not restricted to older adults, as readmission risk among younger patients 18 to 64 years of age may be even higher for selected conditions, such as heart failure.^3,23

Vulnerability after hospitalization is broad. In patients over age 65 initially admitted for heart failure or acute myocardial infarction, only 35% and 10% of readmissions are for recurrent heart failure or reinfarction, respectively.¹ Nearly half of readmissions are for noncardiovascular causes.¹ Similarly, following hospitalization for pneumonia, more than 60 percent of readmissions are for nonpulmonary etiologies. Moreover, the risk for all these causes of readmission is much higher than baseline risk, indicating an extended period of lack of resilience to many types of illness.²⁴ These patterns of broad susceptibility also extend to younger adults hospitalized with common medical conditions.³

Accumulating evidence suggests that hospitalized patients face functional decline, debility, and risk for adverse events despite resolution of the presenting illness, implying perhaps that the hospital environment itself is hazardous to patients’ health. In 1993, Creditor hypothesized that the “hazards of hospitalization,” including enforced bed-rest, sensory deprivation, social isolation, and malnutrition lead to a “cascade of dependency” in which a collection of small insults to multiple organ systems precipitates loss of function and debility despite cure or resolution of presenting illness.¹² Covinsky (2011) later defined hospitalization-associated disability as an iatrogenic hospital-related “disorder” characterized by new impairments in abilities to perform basic activities of daily living such as bathing, feeding, toileting, dressing, transferring, and walking at the time of hospital discharge.¹¹ Others have described a postintensive-care syndrome (PICS),²⁵ characterized by cognitive, psychiatric, and physical impairments acquired during hospitalization for critical illness that persist postdischarge and increase the long-term risk for adverse outcomes, including elevated mortality rates,^26,27 readmission rates,²⁸ and physical disabilities.²⁹ Similar to the “hazards of hospitalization,” PICS is thought to be related to common experiences of ICU stays, including mobility restriction, sensory deprivation, sleep disruption, sedation, malnutrition, and polypharmacy.^30-33

Taken together, these data suggest that adverse health consequences attributable to hospitalization extend across the spectrum of age, presenting disease severity, and hospital treatment location. As detailed below, the PHS hypothesis is rooted in a mechanistic understanding of the role of exogenous stressors in producing physiologic dysregulation and subsequent adverse health effects across multiple organ systems.

Nature of Stress in the Hospital

Compounding the stress of acute illness, hospitalized patients are routinely and repetitively exposed to a wide variety of environmental stressors that may have downstream adverse consequences (Table 1). In the absence of overt clinical manifestations of harm, the possible subclinical physiologic dysfunction generated by the following stress exposures may increase patients’ susceptibility to the manifestations of PHS.

Sleep Disruption

Sleep disruptions trigger potent stress responses,^34,35 yet they are common occurrences during hospitalization. In surveys, about half of patients report poor sleep quality during hospitalization that persists for many months after discharge.³⁶ In a simulated hospital setting, test subjects exposed to typical hospital sounds (paging system, machine alarms, etc.) experienced significant sleep-wake cycle abnormalities.³⁷ Although no work has yet focused specifically on the physiologic consequences of sleep disruption and stress in hospitalized patients, in healthy humans, mild sleep disruption has clear effects on allostasis by disrupting HPA activity, raising cortisol levels, diminishing parasympathetic tone, and impairing cognitive performance.^{18,34,35,38,39}

Malnourishment

Malnourishment in hospitalized patients is common, with one-fifth of hospitalized patients receiving nothing per mouth or clear liquid diets for more than 3 continuous days,⁴⁰ and one-fifth of hospitalized elderly patients receiving less than half of their calculated nutrition requirements.⁴¹ Although the relationship between food restriction, cortisol levels, and postdischarge outcomes has not been fully explored, in healthy humans, meal anticipation, meal withdrawal (withholding an expected meal), and self-reported dietary restraint are known to generate stress responses.^42,43 Furthermore, malnourishment during hospitalization is associated with increased 90-day and 1-year mortality after discharge,⁴⁴ adding malnourishment to the list of plausible components of hospital-related stress.

Mobility Restriction

Physical activity counterbalances stress responses and minimizes downstream consequences of allostatic load,¹⁵ yet mobility limitations via physical and chemical restraints are common in hospitalized patients, particularly among the elderly.^45-47 Many patients are tethered to devices that make ambulation hazardous, such as urinary catheters and infusion pumps. Even without physical or chemical restraints or a limited mobility order, patients may be hesitant to leave the room so as not to miss transport to a diagnostic study or an unscheduled physician’s visit. Indeed, mobility limitations of hospitalized patients increase the risk for adverse events after discharge, while interventions designed to encourage mobility are associated with improved postdischarge outcomes.^47,48

Other Stressors

Other hospital-related aversive stimuli are less commonly quantified, but clearly exist. According to surveys of hospitalized patients, sources of emotional stress include social isolation; loss of autonomy and privacy; fear of serious illness; lack of control over activities of daily living; lack of clear communication between treatment team and patients; and death of a patient roommate.^49,50 Furthermore, consider the physical discomfort and emotional distress of patients with urinary incontinence awaiting assistance for a diaper or bedding change or the pain of repetitive blood draws or other invasive testing. Although individualized, the subjective discomfort and emotional distress associated with these experiences undoubtedly contribute to the stress of hospitalization.

Animal Models of Stress

Laboratory techniques reminiscent of the numerous environmental stressors associated with hospitalization have been used to reliably trigger allostatic overload in healthy young animals.⁵¹ These techniques include sequential exposure to aversive stimuli, including food and water deprivation, continuous overnight illumination, paired housing with known and unknown cagemates, mobility restriction, soiled cage conditions, and continuous noise. All of these techniques have been shown to cause HPA axis and ANS dysfunction, allostatic overload, and subsequent stress-mediated consequences to multiple organ systems.^19,52-54 Given the remarkable similarity of these protocols to common experiences during hospitalization, animal models of stress may be useful in understanding the spectrum of maladaptive consequences experienced by patients within the hospital (Figure 1).

These animal models of stress have resulted in a number of instructive findings. For example, in rodents, extended stress exposure induces structural and functional remodeling of neuronal networks that precipitate learning and memory, working memory, and attention impairments.^55-57 These exposures also result in cardiovascular abnormalities, including dyslipidemia, progressive atherosclerosis,^58,59 and enhanced inflammatory cytokine expression,⁶⁰ all of which increase both atherosclerotic burden and susceptibility to plaque rupture, leading to elevated risk for major cardiovascular adverse events. Moreover, these extended stress exposures in animals increase susceptibility to both bacterial and viral infections and increase their severity.^16,61 This outcome appears to be driven by a stress-induced elevation of glucocorticoid levels, decreased leukocyte proliferation, altered leukocyte trafficking, and a transition to a proinflammatory cytokine environment.^{16, 61} Allostatic overload has also been shown to contribute to metabolic dysregulation involving insulin resistance, persistence of hyperglycemia, dyslipidemia, catabolism of lean muscle, and visceral adipose tissue deposition.^62-64 In addition to cardiovascular, immune, and metabolic consequences of allostatic overload, the spectrum of physiologic dysfunction in animal models is broad and includes mood disorder symptoms,⁶⁵ intestinal barrier abnormalities,⁶⁶ airway reactivity exacerbation,⁶⁷ and enhanced tumor growth.⁶⁸

Although the majority of this research highlights the multisystem effects of variable stress exposure in healthy animals, preliminary evidence suggests that aged or diseased animals subjected to additional stressors display a heightened inflammatory cytokine response that contributes to exaggerated sickness behavior and greater and prolonged cognitive deficits.⁶⁹ Future studies exploring the consequences of extended stress exposure in animals with existing disease or debility may therefore more closely simulate the experience of hospitalized patients and perhaps further our understanding of PHS.

Hospitalized Patients

While no intervention studies have examined the effects of potential hospital stressors on the development of allostatic overload, there is evidence from small studies that dysregulated stress responses during hospitalization are associated with adverse events. For example, high serum cortisol, catecholamine, and proinflammatory cytokine levels during hospitalization have individually been associated with the development of cognitive dysfunction,^70-72 increased risk of cardiovascular events such as myocardial infarction and stroke in the year following discharge,^73-76 and the development of wound infections after discharge.⁷⁷ Moreover, elevated plasma glucose during admission for myocardial infarction in patients with or without diabetes has been associated with greater in-hospital and 1-year mortality,⁷⁸ with a similar relationship seen between elevated plasma glucose and survival after admission for stroke⁷⁹ and pneumonia.⁸⁰ Furthermore, in addition to atherothrombosis, stress may contribute to the risk for venous thromboembolism,⁸¹ resulting in readmissions for deep vein thrombosis or pulmonary embolism posthospitalization. Although potentially surrogate markers of illness acuity, a handful of studies have shown that these stress biomarkers are actually only weakly correlated with,⁸² or independent of,^72,76 disease severity. As discussed in detail below, future studies utilizing a summative measure of multisystem physiologic dysfunction as opposed to individual biomarkers may more accurately reflect the cumulative stress effects of hospitalization and subsequent risk for adverse events.

Additional Considerations

Elderly patients, in particular, may have heightened susceptibility to the consequences of allostatic overload due to common geriatric issues such as multimorbidity and frailty. Patients with chronic diseases display both baseline HPA axis abnormalities as well as dysregulated stress responses and may therefore be more vulnerable to hospitalization-related stress. For example, when subjected to psychosocial stress, patients with chronic conditions such as diabetes, heart failure, or atherosclerosis demonstrate elevated cortisol levels, increased circulating markers of inflammation, as well as prolonged hemodynamic recovery after stress resolution compared with normal controls.^83-85 Additionally, frailty may affect an individual’s susceptibility to exogenous stress. Indeed, frailty identified on hospital admission increases the risk for adverse outcomes during hospitalization and postdischarge.⁸⁶ Although the specific etiology of this relationship is unclear, persons with frailty are known to have elevated levels of cortisol and other inflammatory markers,^87,88 which may contribute to adverse outcomes in the face of additional stressors.

A large body of evidence stretching from bench to bedside suggests that environmental stressors associated with hospitalization are toxic. Understanding PHS within the context of hospital-induced allostatic overload presents a unifying theory for the interrelated multisystem dysfunction and increased susceptibility to adverse events that patients experience after discharge (Figure 2). Furthermore, it defines a potential pathophysiological mechanism for the cognitive impairment, elevated cardiovascular risk, immune system dysfunction, metabolic derangements, and functional decline associated with PHS. Additionally, this theory highlights environmental interventions to limit PHS development and suggests mechanisms to promote stress resilience. Although it is difficult to disentangle the consequences of the endogenous stress triggered by an acute illness from the exogenous stressors related to hospitalization, it is likely that the 2 simultaneous exposures compound risk for stress system dysregulation and allostatic overload. Moreover, hospitalized patients with preexisting HPA axis dysfunction at baseline from chronic disease or advancing age may be even more susceptible to these adverse outcomes. If this hypothesis is true, a reduction in PHS would require mitigation of the modifiable environmental stressors encountered by patients during hospitalization. Directed efforts to diminish ambient noise, limit nighttime disruptions, thoughtfully plan procedures, consider ongoing nutritional status, and promote opportunities for patients to exert some control over their environment may diminish the burden of extrinsic stressors encountered by all patients in the hospital and improve outcomes after discharge.

Hospitals are increasingly recognizing the importance of improving patients’ experience of hospitalization by reducing exposure to potential toxicities. For example, many hospitals are now attempting to reduce sleep disturbances and sleep latency through reduced nighttime noise and light levels, fewer nighttime interruptions for vital signs checks and medication administration, and commonsensical interventions like massages, herbal teas, and warm milk prior to bedtime.⁸⁹ Likewise, intensive care units are targeting environmental and physical stressors with a multifaceted approach to decrease sedative use, promote healthy sleep cycles, and encourage exercise and ambulation even in those patients who are mechanically ventilated.³⁰ Another promising development has been the increase of Hospital at Home programs. In these programs, patients who meet the criteria for inpatient admission are instead comprehensively managed at home for their acute illness through a multidisciplinary effort between physicians, nurses, social workers, physical therapists, and others. Patients hospitalized at home report higher levels of satisfaction and have modest functional gains, improved health-related quality of life, and decreased risk of mortality at 6 months compared with hospitalized patients.^90,91 With some admitting diagnoses (eg, heart failure), hospitalization at home may be associated with decreased readmission risk.⁹² Although not yet investigated on a physiologic level, perhaps the benefits of hospital at home are partially due to the dramatic difference in exposure to environmental stressors.

A tool that quantifies hospital-associated stress may help health providers appreciate the experience of patients and better target interventions to aspects of their structure and process that contribute to allostatic overload. Importantly, allostatic overload cannot be identified by one biomarker of stress but instead requires evidence of dysregulation across inflammatory, neuroendocrine, hormonal, and cardiometabolic systems. Future studies to address the burden of stress faced by hospitalized patients should consider a summative measure of multisystem dysregulation as opposed to isolated assessments of individual biomarkers. Allostatic load has previously been operationalized as the summation of a variety of hemodynamic, hormonal, and metabolic factors, including blood pressure, lipid profile, glycosylated hemoglobin, cortisol, catecholamine levels, and inflammatory markers.⁹³ To develop a hospital-associated allostatic load index, models should ideally be adjusted for acute illness severity, patient-reported stress, and capacity for stress resilience. This tool could then be used to quantify hospitalization-related allostatic load and identify those at greatest risk for adverse events after discharge, as well as measure the effectiveness of strategic environmental interventions (Table 2). A natural first experiment may be a comparison of the allostatic load of hospitalized patients versus those hospitalized at home.

Ketorolac administered during primary tumor surgery may cut risk of distant recurrences in patients with breast cancer, results of a retrospective study show.

Overweight patients appeared most likely to benefit from interoperative treatment with this nonsteroidal anti-inflammatory drug, study investigators reported.

“This approach could be extremely appealing for parts of the globe where obesity has been strongly increasing during the last decade and where resources for cancer treatment are scarce,” they wrote. The report was published in the Journal of the National Cancer Institute.

Ketorolac inhibits enzymes upregulated by leptin, a hormone abnormally secreted in the setting of overweight or obesity, which might explain the concentration of benefit in high–body mass index individuals, noted Christine Desmedt, PhD, of the Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Brussels, and her coauthors.

Indeed, the study also showed no benefit to intraoperative administration of another NSAID, diclofenac, which does not appear to have the same enzyme-inhibitory effects as ketorolac, the investigators said.

This recently published analysis by Dr. Desmedt and her colleagues was based on two retrospective series of patients: one evaluating intraoperative ketorolac in 529 patients versus 298 patients who received no ketorolac, and one evaluating intraoperative diclofenac in 787 patients, versus 220 who did not receive that NSAID.

The investigators found a significant association between ketorolac given during surgery and decreased incidence of distant metastasis (adjusted hazard ratio [aHR], 0.59, 95% confidence interval, 0.37-0.96, P = .03). Reduced recurrence was most evident in patients with high BMI (aHR, 0.55; 95% CI, 0.31-0.96; P = .04).

SOURCE: Desmedt C et al. J Natl Cancer Inst. 2018 Apr 30. doi: 10.1093/jnci/djy042.

Ketorolac administered during primary tumor surgery may cut risk of distant recurrences in patients with breast cancer, results of a retrospective study show.

Overweight patients appeared most likely to benefit from interoperative treatment with this nonsteroidal anti-inflammatory drug, study investigators reported.

“This approach could be extremely appealing for parts of the globe where obesity has been strongly increasing during the last decade and where resources for cancer treatment are scarce,” they wrote. The report was published in the Journal of the National Cancer Institute.

Ketorolac inhibits enzymes upregulated by leptin, a hormone abnormally secreted in the setting of overweight or obesity, which might explain the concentration of benefit in high–body mass index individuals, noted Christine Desmedt, PhD, of the Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Brussels, and her coauthors.

Indeed, the study also showed no benefit to intraoperative administration of another NSAID, diclofenac, which does not appear to have the same enzyme-inhibitory effects as ketorolac, the investigators said.

This recently published analysis by Dr. Desmedt and her colleagues was based on two retrospective series of patients: one evaluating intraoperative ketorolac in 529 patients versus 298 patients who received no ketorolac, and one evaluating intraoperative diclofenac in 787 patients, versus 220 who did not receive that NSAID.

The investigators found a significant association between ketorolac given during surgery and decreased incidence of distant metastasis (adjusted hazard ratio [aHR], 0.59, 95% confidence interval, 0.37-0.96, P = .03). Reduced recurrence was most evident in patients with high BMI (aHR, 0.55; 95% CI, 0.31-0.96; P = .04).

SOURCE: Desmedt C et al. J Natl Cancer Inst. 2018 Apr 30. doi: 10.1093/jnci/djy042.

Ketorolac administered during primary tumor surgery may cut risk of distant recurrences in patients with breast cancer, results of a retrospective study show.

Overweight patients appeared most likely to benefit from interoperative treatment with this nonsteroidal anti-inflammatory drug, study investigators reported.

“This approach could be extremely appealing for parts of the globe where obesity has been strongly increasing during the last decade and where resources for cancer treatment are scarce,” they wrote. The report was published in the Journal of the National Cancer Institute.

Ketorolac inhibits enzymes upregulated by leptin, a hormone abnormally secreted in the setting of overweight or obesity, which might explain the concentration of benefit in high–body mass index individuals, noted Christine Desmedt, PhD, of the Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Brussels, and her coauthors.

Indeed, the study also showed no benefit to intraoperative administration of another NSAID, diclofenac, which does not appear to have the same enzyme-inhibitory effects as ketorolac, the investigators said.

This recently published analysis by Dr. Desmedt and her colleagues was based on two retrospective series of patients: one evaluating intraoperative ketorolac in 529 patients versus 298 patients who received no ketorolac, and one evaluating intraoperative diclofenac in 787 patients, versus 220 who did not receive that NSAID.

The investigators found a significant association between ketorolac given during surgery and decreased incidence of distant metastasis (adjusted hazard ratio [aHR], 0.59, 95% confidence interval, 0.37-0.96, P = .03). Reduced recurrence was most evident in patients with high BMI (aHR, 0.55; 95% CI, 0.31-0.96; P = .04).

SOURCE: Desmedt C et al. J Natl Cancer Inst. 2018 Apr 30. doi: 10.1093/jnci/djy042.

Surgical site infections among colorectal surgery patients in Hawaii decreased by approximately 62% after hospital participation in a national safety program.

The Agency for Healthcare Research and Quality (AHRQ) designed the program to reduce surgical site infections (SSIs), which are harmful to patients and expensive for the health care system, wrote Della M. Lin, MD, of Johns Hopkins University, Baltimore, and the department of surgery at the University of Hawaii, Honolulu, and her colleagues.

In a study published in the Journal of the American College of Surgeons, the researchers reviewed data from a statewide intervention conducted at 15 hospitals in Hawaii from January 2013 to June 2015. The intervention included the Comprehensive Unit-based Safety Program and individualized interventions for each hospital to help reduce SSIs. The primary outcome was the number of colorectal SSIs. A secondary outcome of hospital safety culture was assessed using the AHRQ Hospital Survey on Patient Safety Culture. The participating hospitals ranged from a 25-bed critical-access hospital to a 533-bed academic medical center.

Overall, the colorectal SSI rate decreased significantly (from 12% to 5%) from the first quarter of 2013 to the second quarter of 2015, with a significant linear decrease over the study period. The rate of superficial SSIs decreased significantly, falling from 8% to 3%. However, the rate of deep SSIs was not significantly different before and after the intervention program (2% vs. 0%), nor was the organ space SSI rate (3% vs. 2%). The standardized infection ratio decreased from 1.83 to 0.92.

The culture of safety in the hospitals improved, but more modestly, in 10 of 12 areas that were measured over the study period.

The overall perception of patient safety improved from 49% to 53%, teamwork across different units improved from 49% to 54%, management and support for patient safety improved from 53% to 60%, and nonpunitive response to errors improved from 36% to 40%.

In addition, communication and openness improved from 50% to 53%, frequency of reported events improved from 51% to 60%, feedback and communication about errors improved from 52% to 59%, organizational learning and continuous improvement increased from 59% to 70%, teamwork within units improved from 68% to 75%, and expectations and actions by supervisors and managers to promote safety improved from 58% to 64%. Staff responses reflect agreement on improvement in the areas of issues of communication, feedback mechanisms, and teamwork, but the change in culture was not on the order of the SSI change.

The most common interventions to reduce SSIs were the use of reliable chlorhexidine wash or wipe before surgery/surgical prep; appropriate use of antibiotics with respect to selection, dosage, and timing; standardized postsurgical debriefing; and differentiating clean/dirty/clean in the use of anastomosis trays and closing trays.

One bundle component, the implementation of the standard operating room debrief, was found to be of particular value to participants. The investigators noted that debrief questions such as “What went well?” and “What needs to be improved?” had “encouraged new processes of thinking beyond first-order problem solving. The debrief challenge embraced by the teams emphasized that ‘bundles’ did not consist of only technical interventions [e.g. clean/dirty trays, chlorhexidine gluconate wipes in preop], but embedded culture interventions—new processes for problem solving.”

The study findings were limited by several factors, such as the use of public SSI data that were not audited for accuracy and the inability to monitor the reliability of the implementation of the various interventions, the researchers said. In addition, “In this current study, there was a change in SSI rates and a change in safety culture, but correlations between the two were negligible or weak for most domains of safety culture,” they noted. The question of sustainability of the SSI improvement without the concomitant staff support of culture change was not addressed by the investigators.

However, the results suggest that a 62% decrease is robust, and that for some hospitals with a low volume of colorectal cases, “teams could attend to iteratively reduce surgical harm beyond SSI,” the researchers wrote.

The study was supported in part by the AHRQ. Dr. Lin disclosed serving as a board member and as a paid independent contractor to the Hawaii Medical Service Association. Her coauthors had no financial conflicts to disclose.

SOURCE: Lin DM et al. J Am Coll Surg. 2018 May 18. doi: 10.1016/j.jamcollsurg.2018.04.031.